Purpose:
To investigate the effect of macrolactin A (MA) and 7-O-succinyl macrolactin A (SMA) generated from Bacillus polyfermenticus KJS-2 on a rat model of laser-induced choroidal neovascularization (CNV)

Methods:
The anti-angiogenic activity of MA and SMA was evaluated by in vitro tube formation assay of human umbilical vein endothelial cells (HUVECs) and cell migration assay of HUVECs. CNV was induced by laser photocoagulation on Day 0 in eyes of Brown Norway rats. Intraperitoneal injection of MA (10 or 50 mg/kg), SMA (10 or 50 mg/kg), or PBS was done once a day from on Day 0 to Day 6 (prevention arm) or from Day 7 to Day 13 (treatment arm). On Day 7 (prevention arm) or 14 (treatment arm), eyes were enucleated and retinal pigment epithelium-choroid-sclera flat mounts were prepared. Areas of CNV were determined in flat mounts using intravenously administered FITC-dextran and TRITC-BS isolectin labeling, and quantified using an image analysis program.

Results:
MA and SMA effectively inhibited vascular endothelial growth factor-stimulated in vitro tube formation and cell migration of HUVECs. In the prevention arm, the mean area of CNV was reduced by 27.0% and 42.7% in SMA-treated (10 and 50 mg/kg qd, respectively) eyes compared with PBS-treated control eyes on Day 7 (P<0.01). In the treatment arm, the mean area of CNV was reduced by 25.9% and 41.3 % in SMA-treated (10 and 50 mg/kg qd, respectively) eyes compared with PBS-treated control eyes on Day 14 (P<0.01). However, MA treatment did not show significant reduction of CNV area.

Conclusions:
SMA showed the suppression of formation of new, and regression of pre-formed laser-induced CNV. SMA may be a feasible anti-angiogenic treatment for CNV.